Poly (Adp-Ribose) Polymerase-1 (PARP-1) Is a Good Prognostic Marker for Pancreatic/Periampullary Cancers.

IF 16.4 1区化学 Q1 CHEMISTRY, MULTIDISCIPLINARY Accounts of Chemical Research Pub Date : 2024-09-01 Epub Date: 2024-03-27 DOI:10.1097/MPA.0000000000002356

Kwangil Yim, Kyung Jin Seo, Jamshid Abdul-Ghafar, Mohammad Rizwan Alam, Kwang Yeol Paik, Yosep Chong, Ok Ran Shin

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Abstract

Background: Periampullary cancer (PAC) is highly aggressive with no effective adjuvant therapy or prognostic markers. Recently, poly (ADP-ribose) polymerase-1 (PARP-1) has emerged as a target in solid cancers, and its relationship with epithelial-mesenchymal transition (EMT) has been observed. However, the relationship between PARP-1 and EMT in PAC has not explored well.

Materials and methods: We assessed the prognostic significance of PARP-1 in 190 PACs patients and correlated it with EMT markers, including FGF8, FGFR4, MMP2, MMP3, Snail, and ZEB1. Immunohistochemistry for PARP-1 and EMT markers was performed using a tissue microarray.

Results: PARP-1 and FGF8 expression were associated with better survival unlike other solid cancers ( P = 0.006 and P = 0.003), and MMP3 and ZEB1 expression were associated with poor prognosis in multivariate and survival analyses ( P = 0.009 and P < 0.001). In addition, PARP-1 is related negatively to Snail but not related with other EMT markers, implying an independent mechanism between PARP-1 and EMT in PACs. PARP-1 and FGF8 are independent good survival markers in PACs unlike other solid cancers.

Conclusions: PARP-1 and FGF8 in PACs could not be related to the EMT pathway but must be rather understood in light of similar cancer-protective roles. Further studies are required on EMT-associated immune markers in PACs.

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聚（ADP-核糖）聚合酶-1（PARP-1）是胰腺癌/髓周癌的良好预后标志物。

背景：髓周癌（PAC）具有高度侵袭性，目前尚无有效的辅助治疗或预后标志物。最近，多聚（ADP-核糖）聚合酶-1（PARP-1）已成为实体瘤的靶点，其与上皮-间质转化（EMT）的关系也已被观察到。然而，PARP-1与PAC中EMT的关系尚未得到很好的探讨：方法：我们评估了 190 例 PAC 患者中 PARP1 的预后意义，并将其与 EMT 标志物（包括 FGF8、FGFR4、MMP2、MMP3、Snail 和 ZEB1）相关联。使用组织芯片对PARP-1和EMT标记物进行了免疫组化：结果：与其他实体瘤不同，PARP-1和FGF8的表达与较好的生存率相关（P = 0.006和P = 0.003），而在多变量和生存率分析中，MMP3和ZEB1的表达与不良预后相关（P = 0.009和P < 0.001）。此外，PARP-1与Snail呈负相关，但与其他EMT标记物无关，这意味着PARP-1与PACs中的EMT之间存在独立机制。与其他实体瘤不同，PARP-1和FGF8在PAC中是独立的良好生存标志物：结论：PARP-1和FGF8在PAC中的作用与EMT通路无关，但必须从类似的癌症保护作用角度加以理解。关于PAC中与EMT相关的免疫标记物，还需要进一步研究。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Accounts of Chemical Research 化学-化学综合

CiteScore

31.40

自引率

1.10%

发文量

312

审稿时长

2 months

期刊介绍： Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.